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hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion

  • Authors:
    • Yoshitaka Kamino
    • Yoshihito Kurashige
    • Osamu Uehara
    • Jun Sato
    • Michiko Nishimura
    • Koki Yoshida
    • Toshiya Arakawa
    • Hiroki Nagayasu
    • Masato Saitoh
    • Yoshihiro Abiko
  • View Affiliations / Copyright

    Affiliations: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan, Division of Pediatric Dentistry, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan, Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan, Division of Biochemistry, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan, Division of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061-0293, Japan
    Copyright: © Kamino et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 462-468
    |
    Published online on: June 12, 2014
       https://doi.org/10.3892/or.2014.3260
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Abstract

Human β-defensin-2 (hBD-2) is a type of epithelial antimicrobial peptide. The expression level of hBD-2 mRNA is lower in oral carcinoma cells (OCCs) than in healthy oral epithelium. Yet, it is still unknown how hBD-2 expression is downregulated in OCCs. The present study investigated DNA hypermethylation of hBD-2 in OCCs and the effect of the demethylation and increased expression of hBD-2 on cell proliferation and invasion. Six different types of oral carcinoma cell lines (OSC-19, BSC-OF, SAS, HSC-2, HSC-4 and HSY) and normal oral keratinocytes (NOKs) were used. The expression levels of hBD-2 in all OCCs were significantly lower than that in the NOKs. Treatment with DNA methyltransferase inhibitor, 5-aza-dC, at the concentration of 50 µM significantly induced upregulation of expression of hBD-2 in the OCCs. Using methylation-specific PCR, DNA hypermethylation was observed in all OCCs. These results suggest that DNA hypermethylation is, at least in part, involved in the decreased expression of hBD-2 in OCCs. We examined the effect of 5-aza-dC on the cell proliferation and invasive ability of OCCs. The cell invasion assays showed that the number of OCCs treated with 5-aza-dC on the filters was significantly lower than that of the controls. We examined whether increased expression of hBD-2 generated by gene transfection inhibited the proliferation and invasion of SAS cells. The number of SAS cells exhibiting increased expression of hBD-2 on the filters in the invasion assay were significantly lower on day 7 when compared with the control. hBD-2 may function as a tumor suppressor. Increased expression of hBD-2 induced by demethylation or increased expression generated by gene transfection may be useful therapeutic methods for oral carcinoma.
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Copy and paste a formatted citation
Spandidos Publications style
Kamino Y, Kurashige Y, Uehara O, Sato J, Nishimura M, Yoshida K, Arakawa T, Nagayasu H, Saitoh M, Abiko Y, Abiko Y, et al: hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion. Oncol Rep 32: 462-468, 2014.
APA
Kamino, Y., Kurashige, Y., Uehara, O., Sato, J., Nishimura, M., Yoshida, K. ... Abiko, Y. (2014). hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion. Oncology Reports, 32, 462-468. https://doi.org/10.3892/or.2014.3260
MLA
Kamino, Y., Kurashige, Y., Uehara, O., Sato, J., Nishimura, M., Yoshida, K., Arakawa, T., Nagayasu, H., Saitoh, M., Abiko, Y."hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion". Oncology Reports 32.2 (2014): 462-468.
Chicago
Kamino, Y., Kurashige, Y., Uehara, O., Sato, J., Nishimura, M., Yoshida, K., Arakawa, T., Nagayasu, H., Saitoh, M., Abiko, Y."hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion". Oncology Reports 32, no. 2 (2014): 462-468. https://doi.org/10.3892/or.2014.3260
Copy and paste a formatted citation
x
Spandidos Publications style
Kamino Y, Kurashige Y, Uehara O, Sato J, Nishimura M, Yoshida K, Arakawa T, Nagayasu H, Saitoh M, Abiko Y, Abiko Y, et al: hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion. Oncol Rep 32: 462-468, 2014.
APA
Kamino, Y., Kurashige, Y., Uehara, O., Sato, J., Nishimura, M., Yoshida, K. ... Abiko, Y. (2014). hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion. Oncology Reports, 32, 462-468. https://doi.org/10.3892/or.2014.3260
MLA
Kamino, Y., Kurashige, Y., Uehara, O., Sato, J., Nishimura, M., Yoshida, K., Arakawa, T., Nagayasu, H., Saitoh, M., Abiko, Y."hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion". Oncology Reports 32.2 (2014): 462-468.
Chicago
Kamino, Y., Kurashige, Y., Uehara, O., Sato, J., Nishimura, M., Yoshida, K., Arakawa, T., Nagayasu, H., Saitoh, M., Abiko, Y."hBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion". Oncology Reports 32, no. 2 (2014): 462-468. https://doi.org/10.3892/or.2014.3260
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